A possible new treatment for HIV on the horizon
Promising news regarding treatment of HIV came out of Brazil on the 7th of July. After participating in a trial study in 2015, the São Paulo Patient is the third person to ever be cured of HIV, joining the cohort of the Berlin Patient and the London Patient. However, the São Paulo Patient brings a novel approach to curing HIV, as his treatment is different to the previous two patients.
The Berlin Patient and the London Patient
The treatments for the Berlin and London Patients are based on the mutation of a cell receptor called CCR5, which HIV binds under normal conditions, allowing it to enter the host’s cells. The mutated cell receptor does not allow the virus to enter the host cell, protecting the host from HIV infection. Individuals who carry this mutation are almost fully resistant to HIV infection and do not suffer from many of the symptoms, such as a weakened immune response.
In 2008, the Berlin Patient, Timothy Ray Brown, was the first person to ever be cured of an HIV infection. He was HIV+ and suffering from acute myeloid leukaemia. To treat both conditions, his clinical team devised a course of highly aggressive treatment that involved whole-body radiation and the transplantation of blood cell stem cells from a donor carrying the mutated CCR5 receptor.
The whole-body radiation treatment cleared the Berlin Patient’s original immune cells. The following transplantation of blood cell stem cells meant that the patient’s immune system could be rebuilt using the new cells containing the mutated CCR5 receptor. The theory underlying this treatment is that the new cells and their descendants would be cancer-free and resistant to HIV infection, therefore, addressing both of the patient’s conditions.
Following the treatment, no active HIV was found, and the patient’s immune system was restored. As of July 2020, the Berlin Patient continues to be HIV-free.
In 2017, the London Patient, Adam Castillejo, was the second person to ever be cured of an HIV infection. He was HIV+ and suffering from treatment-resistant Hodgkin’s lymphoma. He was also treated with a blood cell stem cell transplant from a donor with the mutated CCR5 receptor. His treatment was less aggressive than the Berlin Patient’s, as it involved no rounds of whole-body radiation. As of July 2020, the London Patient continues to be HIV-free and is in long-term remission.
Scaling up
The CCR5 receptor mutation was a critical component to successfully cure the Berlin and London Patients. However, it is a highly unique therapy that is unlikely to be successful in settings where resources are limited. The treatment is not only costly, but it is also highly aggressive, with low success rates. Nevertheless, research is being undertaken to investigate whether the CCR5 receptor mutation could be adapted and expanded for large-scale treatment.
The São Paulo Patient
The long-term remission of the São Paulo Patient presents the possibility that a new treatment that could be scaled-up and applied to many individuals in resource-limited settings has been found.
The São Paulo Patient is a 36-year-old man, who remains anonymous to protect his privacy. He was HIV+ and had no other underlying health issues, unlike the Berlin and London Patients. He was treated with an aggressive combination of antiretroviral drugs (ARVs) and nicotinamide.
ARVs are used to treat infection by retroviruses, such as HIV. Retroviruses are viruses which can insert their genetic information into the host cell, thus changing the DNA sequence in the infected cell. There are many classes of ARVs, each targeting different stages of the infection cycle.
The São Paulo Patient was treated with five ARVs, to make sure that any virus particles that might have survived standard treatment were being targeted. Additionally, the São Paulo Patient was given nicotinamide, a form of vitamin B3. In theory, the nicotinamide induces infected cells to activate any latent HIV present in the infected cell’s genetic material. Once the virus is activated and produces new HIV molecules, the cells self-destruct or become vulnerable to action by the immune system.
The São Paulo Patient has been HIV-free for 67 weeks. Following sensitive testing for viral genetic material, no HIV was found in the blood of the patient. Furthermore, a test involving the detection of cells susceptible to HIV infection, found that there were no newly infected cells.
Looking forwards
While the São Paulo Patient’s success story is inspiring, it is important to look at the other participants in the study. Of all five participants, only the São Paulo Patient was cured of HIV, while the other four participants continued to be HIV+ at the conclusion of the trial.
Furthermore, many questions need to be answered before this avenue of treatment is pursued further. The immediacy with which the São Paulo Patient started taking ARVs following HIV infection is unknown, as this occurred before the trial. Additionally, confirmation of exactly when he stopped taking ARVs during the trial is pending. Finally, questions about the treatment itself including how the nicotinamide works and how it induces the activation of latent HIV in infected cells must be investigated fully.
While the possibility of a new treatment which can fight off HIV is exciting, some experts are also calling for a larger number of participants in remission following these trials, stating that, in order to move forward, we must focus not only on individual cases of HIV remission but on substantiated long-term remission in multiple cases.
Written by Cristina Huguet Suárez and edited by Tara Wagner-Gamble.
Cristina’s thoughts… The curing of the São Paulo Patient is wonderful news and shows that we are slowly inching closer to finding a treatment that could cure HIV+ individuals. This treatment is promising as the drugs used are available in most settings. However, the low success rate indicates that it doesn’t seem to be a cure that could be expanded for large-scale treatment. Looking forward, there needs to be a focus on larger success rates in trials, and treatments should ideally be relatively inexpensive and easy to scale-up.
Find me on… LinkedIn @Cristina Huguet Suárez
